Genetic screening for hereditary transthyretin amyloidosis with polyneuropathy in western Sicily : Two years of experience in a neurological clinic
© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology..
BACKGROUND AND PURPOSE: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils.
METHODS: A prospective systematic genetic screening for ATTRv-PN was proposed in patients presenting with a sensory-motor idiopathic polyneuropathy and two or more "red flags" among the following: family history of polyneuropathy or cardiopathy, bilateral carpal tunnel syndrome, cardiac insufficiency, renal amyloidosis, lumbar tract stenosis, autonomic dysfunction, idiopathic gastrointestinal disease, amyloid deposits on biopsy, and vitreous opacities. The detection rate was calculated, and nonparametric analyses were carried out to underline differences among screened positive versus negative patients.
RESULTS: In the first step, 145 suspected patients underwent genetic testing, revealing a diagnosis of ATTRv-PN in 14 patients (10%). Then, cascade screening allowed early recognition of 33 additional individuals (seven symptomatic ATTRv-PN patients and 26 presymptomatic carriers) among 84 first-degree relatives. Patients with a positive genetic test presented a higher frequency of unexplained weight loss, gastrointestinal symptoms, and family history of cardiopathy.
CONCLUSIONS: A systematic screening for ATTRv-PN yielded an increased recognition of the disease in our neurological clinic. Unexplained weight loss associated with axonal polyneuropathy had the highest predictive value in the guidance of clinical suspicion. A focused approach for the screening of ATTRv-PN could lead to an earlier diagnosis and identification of asymptomatic carriers, who will be promptly treated after a strict follow-up at the clinical onset.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
European journal of neurology - 31(2024), 1 vom: 14. Jan., Seite e16065 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Di Stefano, Vincenzo [VerfasserIn] |
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| Links: |
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| Themen: |
Amyloid |
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| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 30.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/ene.16065 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM362218307 |
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| 100 | 1 | |a Di Stefano, Vincenzo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genetic screening for hereditary transthyretin amyloidosis with polyneuropathy in western Sicily |b Two years of experience in a neurological clinic |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. | ||
| 520 | |a BACKGROUND AND PURPOSE: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils | ||
| 520 | |a METHODS: A prospective systematic genetic screening for ATTRv-PN was proposed in patients presenting with a sensory-motor idiopathic polyneuropathy and two or more "red flags" among the following: family history of polyneuropathy or cardiopathy, bilateral carpal tunnel syndrome, cardiac insufficiency, renal amyloidosis, lumbar tract stenosis, autonomic dysfunction, idiopathic gastrointestinal disease, amyloid deposits on biopsy, and vitreous opacities. The detection rate was calculated, and nonparametric analyses were carried out to underline differences among screened positive versus negative patients | ||
| 520 | |a RESULTS: In the first step, 145 suspected patients underwent genetic testing, revealing a diagnosis of ATTRv-PN in 14 patients (10%). Then, cascade screening allowed early recognition of 33 additional individuals (seven symptomatic ATTRv-PN patients and 26 presymptomatic carriers) among 84 first-degree relatives. Patients with a positive genetic test presented a higher frequency of unexplained weight loss, gastrointestinal symptoms, and family history of cardiopathy | ||
| 520 | |a CONCLUSIONS: A systematic screening for ATTRv-PN yielded an increased recognition of the disease in our neurological clinic. Unexplained weight loss associated with axonal polyneuropathy had the highest predictive value in the guidance of clinical suspicion. A focused approach for the screening of ATTRv-PN could lead to an earlier diagnosis and identification of asymptomatic carriers, who will be promptly treated after a strict follow-up at the clinical onset | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a amyloid | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a neuromuscular | |
| 650 | 4 | |a neuropathy | |
| 650 | 4 | |a neurophysiology | |
| 700 | 1 | |a Lupica, Antonino |e verfasserin |4 aut | |
| 700 | 1 | |a Alonge, Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a Pignolo, Antonia |e verfasserin |4 aut | |
| 700 | 1 | |a Augello, Sofia Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Gentile, Francesca |e verfasserin |4 aut | |
| 700 | 1 | |a Gagliardo, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Giglia, Francesca |e verfasserin |4 aut | |
| 700 | 1 | |a Brinch, Daniele |e verfasserin |4 aut | |
| 700 | 1 | |a Cappello, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Di Lisi, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Novo, Giuseppina |e verfasserin |4 aut | |
| 700 | 1 | |a Borgione, Eugenia |e verfasserin |4 aut | |
| 700 | 1 | |a Scuderi, Carmela |e verfasserin |4 aut | |
| 700 | 1 | |a Brighina, Filippo |e verfasserin |4 aut | |
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